Antifragile Treatment for Efficient Chimerism of Induced Pluripotent Stem Cells Derived Hematopoietic Stem Cells.

Stem Cell Rev Rep

Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, 08826, South Korea.

Published: December 2024

AI Article Synopsis

  • Engraftable hematopoietic stem cells (HSC) can be sourced from bone marrow, umbilical cord blood, and peripheral blood, but finding a matched unrelated donor presents a challenge.
  • The study focused on enhancing the efficiency of producing patient-specific induced pluripotent stem cell-derived hematopoietic stem cells (iHSC) by using an antioxidant treatment (ginsenoside Rg1) and verifying engraftment in mice models.
  • Results showed that iHSC treated with Rg1 had high colony forming efficiency in vitro and successful engraftment in mice conditioned with high doses of busulfan, suggesting a new method for creating HSC that could be used in future transplants and potentially paired with gene-edit

Article Abstract

Engraftable hematopoietic stem cells (HSC) can be obtained from bone marrow, umbilical cord blood, and peripheral blood (PB). However, a major bottleneck in HSC transplantation is identifying an unrelated donor that completely matches the human leukocyte antigen type of the recipient. This issue can be resolved by producing patient-specific stem cells. The purpose of this study was to identify the conditions under which induced pluripotent stem cells (iPSC)-derived hematopoietic stem cells (iHSC) exhibit high efficiency. Because HSC are fragile and vulnerable to damage, this study was performed under the hypothesis that the engraftment rate could be increased by antifragile treatment. Antioxidant ginsenoside Rg1 was used to differentiate from iPSC to iHSC, and differentiated iHSC was intravenously injected into Balb/c nude mouse conditioned with diverse concentrations of busulfan. Engraftment was verified by the presence of human-specific markers in the PB at 2 and 8 weeks post iHSC transplantation. iHSC differentiated by incorporating 1 µM of Rg1 demonstrated high colony forming efficiency in vitro. Additionally, high efficiency engraftment occurred immediately after iHSC were transplanted into mice conditioned with high dose busulfan at a dosage of 125 mg/kg or higher. In this study, high-quality iHSC manufacturing and transplantation conditions capable of high efficiency engraftment in vivo were established. Hereafter, this method of producing HSC using patient-specific iPSC will become the fourth new source of HSC. Additionally, if gene-editing technology is applied, the scope of its application can be expanded to diverse infectious diseases.

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Source
http://dx.doi.org/10.1007/s12015-024-10828-xDOI Listing

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